Muscular dystrophy, hereditary muscular diseases 4.33/5 (3)

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Duchenne muscular dystrophy in a 5- (a), 10- (b) and 16-year-old boy (c, d). Sanzasello I, Int Sch Res Notices, 2014. Openi.

Definition

Muscular dystrophies is a group of hereditary, progressive muscle diseases. The diseases are rare; in total, less than one in 2000 people are attacked (prevalence) (reference; Iolascon G, 2019). Over 30 types of muscular dystrophy are known. Each type of muscular dystrophy has its own genetic inheritance pattern and defects in the specific genes that cause the various disease manifestations (La Pelusa A, 2021). Most typical is gradually increasing muscle weakness. Muscular dystrophy is distinguished from the typically inflammatory ones myositis, metabolic disease with muscle manifestations (metabolic myopathies), mitochondrial disease, chemical damage (toxic myopathy) and muscle manifestations of another underlying disease (secondary myopathy). Genetic testing is possible for several of the muscular dystrophies (genportalen.no). 

Disease Cause

The diseases are caused by DNA mutations where deletions cause loss of DNA, while point mutations cause changes in the code. The mutations affect proteins localized to the muscle cell.

Symptoms

The muscular dystrophies have different clinical symptoms and examination findings. Some develop large but progressively weaker muscles (pseudohypertrophy), while other types result in loss of muscle size and loss of strength. In children, limping or difficulty standing up may be noticeable. Other symptoms include breathing problems with reduced respiratory muscles, weak back, heart rhythm disturbances, graceful facial features with reduced facial muscles. Age of onset can provide important diagnostic clues (Guzman OdRC, 2012). Increasing symptoms can occur in childhood, but several types begin in the 20s-40s (Guzman OdRC, 2012).

Examinations

Disease history: Family/inheritance. Dominant symptoms: weakness, pain or stiffness? Other: Age of onset, time over which the symptoms have developed, drug consumption (statins, others) and any symptoms of systemic connective tissue diseases or metabolic diseases.

Clinical examinations should include a general examination of the skin, eyes, nerves, lungs, heart with rhythm/frequency and other organs. The musculature is assessed in particular; shoulders, neck, pelvis, hips, thighs (proximal muscles) or forearms, hands, calves, feet (distal muscles), both arms/legs (symmetric / asymmetric distribution?) Large muscles (hypertrophy) or muscle wasting (atrophy)? Twitching in muscles (Fasciculations)? The problem with getting up from squatting? - Test of muscle strength. Standardized tests of muscle strength and endurance can be performed by trained physiotherapists.

Laboratory tests. Apart from slightly to moderately elevated muscle enzymes (CK, LD, AST), no special results are expected. To rule out similar conditions, tests may include CRP, SR, Hgb, leukocytes with differential counts, electrolytes, liver, kidney and thyroid function tests and glucose. If a cardiac manifestation is suspected, troponin may also be relevant. Cortisol (morning value) is relevant if adrenal gland over- or under-functioning is suspected. Antinuclear antibodies (ANA) supplemented with myositis-specific and associated antibodies may be applicable. Urine sting.

Imaging, MR examination of the thigh muscles or where the symptoms are most evident gives the greatest chance of seeing changes; fat infiltration and muscle wasting (atrophy) speak for typical chronic changes, while marked fluid/edema may speak for myositis, but is not specific. MRI of muscles is also used to locate a suitable site for biopsy. A CT of the lungs can be done to rule out muscle disease with pulmonary manifestations and an X-ray of the esophagus (filming while swallowing a contrast agent) examines the function of the oesophageal muscles.

Electromyography (EMG) can distinguish between neurogenic (non-inflammatory) and inflammatory muscular (myositis) damage.

ECG is applicable in case of possible cardiac manifestation.

Tissue sample (biopsy) is important to distinguish typical changes from inflammation, metabolic/storage disease or other similar conditions.

Treatment

To improve the prognosis, everyone is recommended to emphasize a healthy lifestyle as early as possible. One should continuously make arrangements to retain muscle strength through optimal nutrition and individually adapted physical training and activity. A physiotherapist with expertise in muscle diseases will be useful for individual advice and follow-up. Based on which gene error is present, several new drugs are being tested. Gene therapy will probably also become available for several types of muscular dystrophy (reference: Iolascon G, 2019).

Different types of muscular dystrophy

Limb-girdle

  • Most often begins between 10 and 30 years of age, most often among boys. Several types. The most severe forms have the earliest onset.
  • Genetic testing is possible. Several genetic variants of the disease. More here (Genetikkportalen.no)
    • Spontaneous mutation in the CAV3 gene and partial caveolin3 deficiency with high creatine kinase (CK) in blood samples but without muscle failure occurring
  • Scapulo-humoral (shoulder-upper arm) type
  • Pelvi-femoral type
  • Autosomal recessive and dominant types
  • Creatine kinase (CK) in blood is elevated

Duchenne Muscular Dystrophy

  • Detected in childhood (genetic test)
    • Delayed development of gait function (runs at approx. 2 years of age)
    • From the 3-4 age, trouble jumping, running, staircases occurs
    • Often enlarged leg muscles
    • From 5-8 years: waddling
  • X-linked recessive inheritance: Almost only boys get sick. Women are carriers of disease predisposition (most often without symptoms). Amniotic fluid diagnostics in pregnancy is possible
  • Mutation in the DMD gene (on chromosome Xp21)
  • Occurrence: 1 per 3.500-6000 newborn boys
  • About. 10% develops isolated cardiomyopathy (heart disease)

Becker Muscular Dystrophy

  • Most often boys (X-linked, recessive inheritance)
  • Onset of the disease between 8–25 years, sometimes later
  • The pelvis and thigh muscles weaken, the chest muscles and upper arms become thinner (muscle wasting).
  • Muscle biopsy with immunohistochemical testing on muscular dystrophies
  • Gene test. Genetic testing here (Genetikkportalen.no)

Facio-scapular

  • The disease typically begins between the ages of 15 and 30. By the age of 20, 90% have typical features. Cases in young children and elderly people have also been seen.
  • Muscular weakness in the face, scapula, upper arm, calfs
  • Not necessarily equal manifestations on both sides of the body (asymmetrical manifestation)
  • Pain in 55-80%,
  • Eye manifestation in the retina with visual disturbances in 50-75%.
  • Hearing Loss
  • Abnormal heart rhythms
  • Cognitive problems

Myotonic dystrophy

Emery-Dreifuss dystrophy

Hereditary Metabolic Myopathies

  • Carbohydrate and lipid metabolism
  • Test blood samples on lactate, pyruvate, LD, uric acid, soluble and total carnitine, ketones, glucose, ammonia, myoglobin, liver transaminases, potassium, calcium, phosphate, creatinine, acylcarnitine
  • Test urine on ketones, myoglobin, dicarboxylic acids, acylglycines
  • EMG
  • Ischemic and aerobic load tests
  • Muscle Biopsy
  • DNA genetic testing

Similar conditions / differential diagnoses

Literature


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